Human fibulin-4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues
Human fibulin-4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues
复制标题
DOI：
10.1016/s0014-5793(00)02389-9
复制
发表时间：
2001-01-26
期刊：
影响因子：
3.5
通讯作者：
Conseiller, E
中科院分区：
文献类型：
--
作者：
Gallagher, WM;Greene, LM;Conseiller, E
在这里，我们报告了一个人的fibulin-4的直系同源物的鉴定，沿着其生物合成过程和mRNA在正常和肿瘤组织中的表达水平的分析。fibulin-4 cDNA的比较序列分析揭示了信号序列的明显多态性，这可以解释先前报道的fibulin-4转染子的低效分泌。纤蛋白-4 mRNA的体外翻译揭示了全长和截短多肽的存在，后者显然是从替代翻译起始位点产生的。由于该多肽未能掺入内质网膜制剂中，因此得出结论，它缺乏信号序列，因此可能代表细胞内形式的fibulin-4。使用荧光原位杂交分析，人类fibulin-4基因定位于染色体11 q13，该区域与小鼠染色体7和19的部分同线。考虑到11 q13区域的易位、扩增和其他重排与多种人类癌症相关的事实，在一系列结肠肿瘤中评价了人纤蛋白-4的表达。逆转录-聚合酶链反应分析配对人结肠肿瘤和邻近正常组织活检的RNA显示，相当比例的肿瘤在fibulin-4 mRNA表达水平上有相似的2 -7倍的增加。两者合计，这里报道的结果表明，细胞内形式的fibulin-4蛋白可能存在，并且fibulin-1基因的表达失调与人类结肠肿瘤发生相关。(C)2001年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
Here, we report the identification of a human orthologue of fibulin-4, along with analysis of its biosynthetic processing and mRNA expression levels in normal and tumour tissues. Comparative sequence analysis of fibulin-4 cDNAs revealed apparent polymorphisms in the signal sequence that could account for previously reported inefficient secretion in fibulin-4 transfectants. In vitro translation of fibulin-4 mRNA revealed the presence of full-length and truncated polypeptides, the latter apparently generated from an alternative translation initiation site. Since this polypeptide failed to incorporate into endoplasmic reticulum membrane preparations, it was concluded that it lacked a signal sequence and thus could represent an intracellular form of fibulin-4. Using fluorescence in situ hybridisation analysis, the human fibulin-4 gene was localised to chromosome 11q13, this region being syntenic to portions of mouse chromosomes 7 and 19. Considering the fact that translocations, amplifications and other rearrangements of the 11q13 region are associated with a variety of human cancers, the expression of human fibulin-4 was evaluated in a series of colon tumours. Reverse transcription-polymerase chain reaction analysis of RNA from paired human colon tumour and adjacent normal tissue biopsies showed that a significant proportion of tumours had similar to2-7-fold increases in the level of fibulin-4 mRNA expression. Taken together, results reported here suggest that an intracellular form of fibulin-4 protein may exist and that dysregulated expression of the fibulin-1 gene is associated with human colon tumourigenesis. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.